Data accumulated in this laboratory have indicated that spleen cells carrying the H-2Kb allele, which have been sensitized against syngeneic trinitropheynl (TNP)-modified stimulator cells in vitro, display a cytotoxic effect against TNP-modified target cells carrying a mutation in the H-2Kb allele (haplotypes H-2ba, -bd, and -bf. Similar cross reactivity in TNP-CML (cell mediated lympholysis) was observed in the reciprocal direction. Spleen cells carrying the H-2Kk allele and sensitized against TNP-modified syngeneic stimulators displayed a cytotoxic effect against TNP-modified target cells carrying a mutation in the H-2Kk allele and vice versa. In these studies we also characterized the effector cells and showed that they were sensitive to anti-T cell serum in the presence of complement. Further, supernatants from immune cultures did not induce non-immune cells to display a cytotoxic effect. When we titrated the effector cells from the mutant and wild type strains of the H-2b haplotype, we found no detectable quantitative differences in their activities. Together, these data indicate that T cell cross reactivity in the TNP-CML assay can occur in H-2 allogeneic hosts, but only if the H-2 haplotypes between the stimulator and target cells are closely related. BIBLIOGRAPHIC REFERENCES: Forman, J. and Klein, J. Immunogenetic Analysis of H-2 Mutations. IV. Cross-reactivity in Cell-Mediated Lympholysis Between TNP-Modified Cells from H-2 Mutant Strains. Immunogenetics, 4:183-193, 1977. Forman, J., E.S. Vitetta and D.A. Hart. Relationship Between Trinitropheynl and H-2 Antigens on Trinitrophenyl-Modified Spleen Cells. II. Correlation between Derivatization of H-2 Antigens with Trinitrophenyl and the Ability of Trinitrophenyl-Modified Cells to React Functionally in the CML Assay. J. Immunol., 118:803-808, 1977.